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Autoimmune rheumatic diseases comprise a group of immune-related disorders characterized by non-organ-specific inflammation. These diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, among others. Typically involving the hematologic system, these diseases may also affect multiple organs and systems. The pathogenesis of autoimmune rheumatic immune diseases is complex, with diverse etiologies, all associated with immune dysfunction. The current treatment options for this type of disease are relatively limited and come with certain side effects. Therefore, the urgent challenge remains to identify novel therapeutic targets for these diseases. Sterol regulatory element-binding proteins (SREBPs) are basic helix-loop-helix-leucine zipper transcription factors that regulate the expression of genes involved in lipid and cholesterol biosynthesis. The expression and transcriptional activity of SREBPs can be modulated by extracellular stimuli such as polyunsaturated fatty acids, amino acids, glucose, and energy pathways including AKT-mTORC and AMP-activated protein kinase (AMPK). Studies have shown that SREBPs play roles in regulating lipid metabolism, cytokine production, inflammation, and the proliferation of germinal center B (GCB) cells. These functions are significant in the pathogenesis of rheumatic and immune diseases (Graphical abstract). Therefore, this paper reviews the potential mechanisms of SREBPs in the development of SLE, RA, and gout, based on an exploration of their functions. [ABSTRACT FROM AUTHOR]

Objective: to evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine's immune response. Methods: We designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed. Results: Performing a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p<0.05) in the level of the ID50, both for healthy controls and for patients with IMRDs. The humoral response of patients with IMRDs is significantly lower compared to healthy controls for the Omicron variant of SARS-CoV-2 (p = 0.0015). The humoral response of patients with IMRDs decreases significantly when the time interval between vaccination and sample collection is greater than 35 days. This difference was observed in the response, both for the Wuhan variant and for the Omicron variant. Conclusion: The IMRDs patients, the humoral response variation in the SARS-CoV-2 vaccine depends on doses and type of vaccine administered, the humoral response times and the treatment that these patients are receiving. [ABSTRACT FROM AUTHOR]

Introduction: The Coronavirus disease 2019 (COVID-19) pandemic has been the biggest threat to humankind during the last 3 years. It has caused the loss of more than 6.9 million precious lives across the world. The only method by which the massacre could be stopped was by mass vaccination or mass immunization. The patients suffering from autoimmune rheumatic disorders (AIRDs) and treated with immunosuppressants were the high-priority candidates for vaccination. However, the data regarding the efficacy of COVID-19 vaccines in this group of patients are very less. Hence, this study was planned to study the immunogenicity of Covishield in patients with AIRDs attending the rheumatology OPD at DMCH, Ludhiana. Materials and Methods: It was a prospective cohort study and was planned by the Department of Biochemistry and Department of Clinical Immunology and Rheumatology at Dayanand Medical College and Hospital, Ludhiana. Fifty patients with AIRDs attending the DMCH rheumatology OPD and 52 age and sex-matched healthy controls who had received two doses of Covishield vaccine were included in this study. Patients having any other immunosuppressive conditions like uncontrolled diabetes, hepatitis, malignancy or HIV were excluded. Patients who had suffered from previous laboratory-confirmed COVID-19 infection (by RT-PCR) were also excluded. Blood samples were collected following all aseptic precautions from patients and controls on the 28th day after administration of a second dose of Covishield vaccine and total antibodies to the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor binding domain was measured using Elecsys Anti-SARS-CoV-2 S kit from Roche. Results: It was observed that no significant difference was there in antibody titre between cases and controls (6213 ± 4418 vs. 8331 ± 7979, P = 0.1022). It was also observed that no statistically significant difference in antibody titre in cases without prednisolone and those taking treatment with prednisolone was found (P = 0.7058). A similar observation was found in terms of methotrexate also (P = 0.457). No significant difference in antibody titres was there when compared with controls (for prednisolone, P = 0.169, for methotrexate, P = 0.078). We found that only the patients receiving mycophenolate mofetil showed a statistically significant decrease in antibody titre in comparison to healthy controls (P = 0.03). Our study showed no statistically significant difference in antibody titres between patients suffering from different AIRDs. Conclusion: Our study supplements the fact that patients with AIRDs in India can receive Covishield as the primary vaccine against COVID-19 without concerns regarding decreased immunogenicity or increased adverse effects.

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: "vitamin D, muscle, rheumatic diseases." Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020–2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold. [ABSTRACT FROM AUTHOR]

The role of abnormal epigenetic modifications, particularly DNA methylation, in the pathogenesis of autoimmune rheumatic diseases (ARDs) has garnered increasing attention. Lymphocyte dysfunction is a significant contributor to the pathogenesis of ARDs. Methylation is crucial for maintaining normal immune system function, and aberrant methylation can hinder lymphocyte differentiation, resulting in functional abnormalities that disrupt immune tolerance, leading to the excessive expression of inflammatory cytokines, thereby exacerbating the onset and progression of ARDs. Recent studies suggest that methylation-related factors have the potential to serve as biomarkers for monitoring the activity of ARDs. This review summarizes the current state of research on the impact of DNA and RNA methylation on the development, differentiation, and function of T and B cells and examines the progress of these epigenetic modifications in studies of six specific ARDs: systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, juvenile idiopathic arthritis, and ankylosing spondylitis. Additionally, we propose that exploring the interplay between RNA methylation and DNA methylation may represent a novel direction for understanding the pathogenesis of ARDs and developing novel treatment strategies. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionized the treatment landscape of haematological malignancies. The past 2 years has witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis and anti-synthetase syndrome. In comparison with existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promising results necessitate validation through long-term, large-sample randomized controlled studies. Corroborating the role of CAR-T therapy in refractory rheumatological disorders and affirming safety, efficacy and durability of responses are the aims of future clinical studies. Optimizing the engineering strategies and better patient selection are also critical to further refining the successful clinical implementation of CAR-T therapy. [ABSTRACT FROM AUTHOR]

Introduction: The Coronavirus disease 2019 (COVID‑19) pandemic has been the biggest threat to humankind during the last 3 years. It has caused the loss of more than 6.9 million precious lives across the world. The only method by which the massacre could be stopped was by mass vaccination or mass immunization. The patients suffering from autoimmune rheumatic disorders (AIRDs) and treated with immunosuppressants were the high‑priority candidates for vaccination. However, the data regarding the efficacy of COVID‑19 vaccines in this group of patients are very less. Hence, this study was planned to study the immunogenicity of Covishield in patients with AIRDs attending the rheumatology OPD at DMCH, Ludhiana. Materials and Methods: It was a prospective cohort study and was planned by the Department of Biochemistry and Department of Clinical Immunology and Rheumatology at Dayanand Medical College and Hospital, Ludhiana. Fifty patients with AIRDs attending the DMCH rheumatology OPD and 52 age and sex‑matched healthy controls who had received two doses of Covishield vaccine were included in this study. Patients having any other immunosuppressive conditions like uncontrolled diabetes, hepatitis, malignancy or HIV were excluded. Patients who had suffered from previous laboratory‑confirmed COVID‑19 infection (by RT‑PCR) were also excluded. Blood samples were collected following all aseptic precautions from patients and controls on the 28th day after administration of a second dose of Covishield vaccine and total antibodies to the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor binding domain was measured using Elecsys Anti‑SARS‑CoV‑2 S kit from Roche. Results: It was observed that no significant difference was there in antibody titre between cases and controls (6213 ± 4418 vs. 8331 ± 7979, P = 0.1022). It was also observed that no statistically significant difference in antibody titre in cases without prednisolone and those taking treatment with prednisolone was found (P = 0.7058). A similar observation was found in terms of methotrexate also (P = 0.457). No significant difference in antibody titres was there when compared with controls (for prednisolone, P = 0.169, for methotrexate, P = 0.078). We found that only the patients receiving mycophenolate mofetil showed a statistically significant decrease in antibody titre in comparison to healthy controls (P = 0.03). Our study showed no statistically significant difference in antibody titres between patients suffering from different AIRDs. Conclusion: Our study supplements the fact that patients with AIRDs in India can receive Covishield as the primary vaccine against COVID‑19 without concerns regarding decreased immunogenicity or increased adverse effects. [ABSTRACT FROM AUTHOR]

This document provides demographic details and adverse drug reactions associated with low-dose methotrexate therapy in patients with rheumatic diseases. The study analyzed a large cohort of patients with various autoimmune rheumatic diseases and found that low-dose methotrexate with folate supplementation reduced the incidence of adverse effects. Factors such as body mass index, alcohol consumption, and smoking did not have a significant influence on the rate of adverse effects. However, the study acknowledges that definitions of adverse effects may vary among studies and some adverse effects could be due to underlying rheumatic diseases rather than methotrexate use alone. [Extracted from the article]

Objective. Infectious conditions are a significant cause of mortality in autoimmune rheumatic diseases (ARD). Among patients hospitalized with an infection, we compared in-hospital and long-term (3-year) mortality between those with and without ARD. Methods. This retrospective analysis included members of the largest health maintenance organization in Israel, aged > 18 years at the first episode of infection, who required hospitalization during 2003-2019. We compared in-hospital mortality and the results of a 3-year landmark analysis of those who survived the index hospitalization between patients with ARD, according to disease subgroups, and patients without ARD. Additionally, we compared mortality outcomes among patients with ARD, according to subgroup diagnosis, matched in a 1:3 ratio by age, sex, and ethnicity to patients without ARD. Results. Included were 365,247 patients who were admitted for the first time with the diagnosis of a serious infection. Of these, we identified 9755 with rheumatoid arthritis (RA), 1351 with systemic lupus erythematosus, 2120 with spondyloarthritis (SpA), 584 with systemic sclerosis, and 3214 with vasculitis. In a matched multivariate analysis, the risk for in-hospital mortality was lower among patients with RA (odds ratio [OR] 0.89, 95% CI 0.81-0.97) and SpA (OR 0.77, 95% CI 0.63-0.94). In a similar analysis, the risk of 3-year mortality was lower among patients with RA (hazard ratio [HR] 0.82, 95% CI 0.78-0.86) and vasculitis (HR 0.86, 95% CI 0.80-0.93). Conclusion. Among patients hospitalized for an infection, the risk of in-hospital and 3-year mortality was not increased among those with ARD compared to those without ARD. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have investigated a possible correlation between Epstein-Barr virus (EBV) and autoimmune rheumatic diseases (ARDs). However, establishing a cause-and-effect relationship remains a challenging endeavor. This study employs Mendelian randomization to examine the impact of EBV nuclear antigen-1 antibody (EBNA-1) antibody levels on the susceptibility to nine distinct ARDs, including rheumatoid arthritis (RA), primary Sjogren's syndrome (PSS), systemic lupus erythematosus (SLE), undifferentiated reactive arthritis (UA), systemic sclerosis (SSc), adult-onset Still's disease (AOSD), psoriatic arthritis (PsA), dermatomyositis (DM), and ankylosing spondylitis (AS). Methods: The researchers applied a two-sample Mendelian randomization approach, utilizing online data from separate cohorts of European descent. We drew upon data from GWAS related to EBNA-1 antibody levels and the nine autoimmune-related disorders. Our primary analyses predominantly relied on the Inverse Variance Weighted methodology, complemented by a range of sensitivity assessments. Results: Our analysis revealed significant direct associations between EBNA-1 antibody levels and the risk of developing PSS (95 % CI: 0.44 to 0.85, p = 0.003), PsA (95 % CI: 0.36 to 0.99, p = 0.044), AS (95 % CI: 0.07 to 0.88, p = 0.031), and UA (95 % CI: 0.56 to 0.96, p = 0.025). These results remained consistent through comprehensive sensitivity analyses. However, no clear associations were found for the other specified conditions. Conclusions: Our findings provide compelling evidence that EBNA-1 antibody levels play a role in developing ARDs. These findings enhance our understanding of ARD pathogenesis and hold substantial promise for developing potential treatment strategies.

Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of disorders characterized by an inappropriate immune reactivity against different body tissues. Patients affected by ARDs present increased cardiovascular morbidity and mortality, which significantly impacts long-term prognosis. Endothelial dysfunction, inflammation, oxidative stress, and autoimmunity are strictly involved in atherosclerosis progression and coronary microvascular dysfunction (CMD), both of which contribute to increased cardiovascular risk. CMD represents the inability of the coronary microvasculature to respond with vasodilation to increased cardiac metabolic demands and can be assessed by non-invasive and invasive imaging tests. Coronary flow velocity reserve assessed by echocardiography has been demonstrated to accurately identify ARDs patients with CMD. However, stress cardiac magnetic resonance (CMR) accurately assesses myocardial ischemia, perfusion, and viability in ARDs patients. The myocardial perfusion reserve index (MPRI) is a robust semiquantitative imaging marker that represents the vasodilatory capacity of the coronary microcirculation in response to a vasodilator stress. In the absence of significant coronary stenosis, ARDs patients revealed a reduced MPRI in comparison with the general population, regardless of the presence of myocardial fibrosis. Identification of CMD in asymptomatic patients could be crucial to precociously start targeted medical therapy, avoiding major adverse cardiac events in this clinical setting. This review aims to summarize the current evidence regarding CMD in ARDs patients, focusing on the role of stress CMR and the promising myocardial perfusion analysis.

Abstract Background Paxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs). Methods TriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2–5 days of COVID-19 diagnosis were performed. Results Paxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47–0.88]), arrhythmia outcomes (HR = 0.81 [0.68–0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35–0.74]) naming heart failure (HR = 0.41 [0.26–0.63]) and deep vein thrombosis (HR = 0.46 [0.24–0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44–0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66–0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11–0.40]), admission (HR = 0.68 [0.60–0.76]), and ICU admission rates (HR = 0.52 [0.33–0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis. Conclusions Paxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.

Autoimmune rheumatic diseases (ARDs) encompass a diverse array of conditions with varied clinical manifestations affecting multiple body systems. Among young patients with ARD, the most common bone disorders are avascular necrosis (AVN) and osteoporosis. ARDs and glucocorticoid use pose major risk factors for AVN and osteoporosis in this population. Unexplained hip pain should raise suspicion of AVN, warranting further investigation, such as MRI. While traditionally associated with older individuals, osteoporosis should not be overlooked in young adults with ARDs. Assessing fracture risk and implementing appropriate management strategies are crucial. Early recognition and tailored treatment are essential for preserving quality of life. ARDs and glucocorticoid use increase osteoporosis risk. Premenopausal women with conditions like rheumatoid arthritis may experience a 17.1% decrease in femoral neck BMD. Similarly, patients with spondyloarthritis exhibit high osteoporosis rates. Diagnosing and managing osteoporosis in young adults remain challenging, highlighting the importance of fracture prevention. Guidelines offer recommendations for preventing, monitoring, and treating glucocorticoid-induced osteoporosis. Considering prevention, early recognition, and appropriate treatment are vital during the clinical evaluation of young adults. Addressing these aspects improves outcomes and mitigates skeletal comorbidity in ARDs. [ABSTRACT FROM AUTHOR]

Introduction: Current therapies for autoimmune rheumatic diseases (ARDs) have limited efficacy in certain patients, highlighting the need for the development of novel treatment approaches. This meta-analysis aims to assess the efficacy and safety of low-dose interleukin-2 (LD-IL-2) and evaluate the alterations in lymphocyte subsets in various rheumatic diseases following administration of different dosages of LD-IL-2. Methods: A comprehensive search was conducted in PubMed, Web of Science, the Cochrane Library, Embase databases and CNKI to identify relevant studies. A total of 31 trials were included in this meta-analysis. The review protocols were registered on PROSPERO (CRD42022318916), and the study followed the PRISMA guidelines. Results: Following LD-IL-2 treatment, patients with ARDs exhibited a significant increase in the number of Th17 cells and Tregs compared to their pre-treatment levels [standardized mean difference (SMD) = 0.50, 95% confidence interval (CI) (0.33, 0.67), P < 0.001; SMD = 1.13, 95% CI (0.97, 1.29), P < 0.001]. Moreover, the Th17/Tregs ratio showed a significant decrease [SMD = − 0.54, 95% CI (− 0.64, − 0.45), P < 0.001]. In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), LD-IL-2 injection led to a significant increase in Treg numbers, and the Th17/Tregs ratio and disease activity scores, including Disease Activity Score-28 joints (DAS28), Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), were all significantly reduced. No serious adverse events were reported in any of the included studies. Additionally, 54.8% of patients with lupus nephritis achieved distinct clinical remission following LD-IL-2 treatment. Injection site reactions and fever were the most common side effects of LD-IL-2, occurring in 33.1% and 14.4% of patients, respectively. Conclusion: LD-IL-2 treatment showed promise and was well tolerated in the management of ARDs, as it effectively promoted the proliferation and functional recovery of Tregs. Trial Registration: Retrospectively registered (CRD42022318916, 21/04/2022). [ABSTRACT FROM AUTHOR]

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs' diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions. [ABSTRACT FROM AUTHOR]

Objectiveto evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine’s immune response.MethodsWe designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed.ResultsPerforming a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p

BackgroundCurrently, the association between the consumption of polyunsaturated fatty acids (PUFAs) and the susceptibility to autoimmune rheumatic diseases (ARDs) remains conflict and lacks substantial evidence in various clinical studies. To address this issue, we employed Mendelian randomization (MR) to establish causal links between six types of PUFAs and their connection to the risk of ARDs.MethodsWe retrieved summary-level data on six types of PUFAs, and five different types of ARDs from publicly accessible GWAS statistics. Causal relationships were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the reliability of our research findings, we used four complementary approaches and conducted multivariable MR analysis (MVMR). Additionally, we investigated reverse causality through a reverse MR analysis.ResultsOur results indicate that a heightened genetic predisposition for elevated levels of EPA (ORIVW: 0.924, 95% CI: 0.666–1.283, PIVW = 0.025) was linked to a decreased susceptibility to psoriatic arthritis (PsA). Importantly, the genetically predicted higher levels of EPA remain significantly associated with an reduced risk of PsA, even after adjusting for multiple testing using the FDR method (PIVW–FDR–corrected = 0.033) and multivariable MR analysis (PMV-IVW 0.05) and multiple testing using the FDR method (PIVW–FDR–corrected = 0.062). Moreover, effects of total omega-3 PUFAs, DHA, EPA, and LA on PsA, were massively driven by SNP effects in the FADS gene region. Furthermore, no causal association was identified between the concentrations of other circulating PUFAs and the risk of other ARDs. Further analysis revealed no significant horizontal pleiotropy and heterogeneity or reverse causality.ConclusionOur comprehensive MR analysis indicated that EPA is a key omega-3 PUFA that may protect against PsA but not other ARDs. The FADS2 gene appears to play a central role in mediating the effects of omega-3 PUFAs on PsA risk. These findings suggest that EPA supplementation may be a promising strategy for preventing PsA onset. Further well-powered epidemiological studies and clinical trials are warranted to explore the potential mechanisms underlying the protective effects of EPA in PsA.

Abstract Introduction Current therapies for autoimmune rheumatic diseases (ARDs) have limited efficacy in certain patients, highlighting the need for the development of novel treatment approaches. This meta-analysis aims to assess the efficacy and safety of low-dose interleukin-2 (LD-IL-2) and evaluate the alterations in lymphocyte subsets in various rheumatic diseases following administration of different dosages of LD-IL-2. Methods A comprehensive search was conducted in PubMed, Web of Science, the Cochrane Library, Embase databases and CNKI to identify relevant studies. A total of 31 trials were included in this meta-analysis. The review protocols were registered on PROSPERO (CRD42022318916), and the study followed the PRISMA guidelines. Results Following LD-IL-2 treatment, patients with ARDs exhibited a significant increase in the number of Th17 cells and Tregs compared to their pre-treatment levels [standardized mean difference (SMD) = 0.50, 95% confidence interval (CI) (0.33, 0.67), P

The purpose of this investigation is to involve women with autoimmune rheumatic diseases through reading, writing, and spaces where they fortify their inner strength and get them integrated into society; since they have lived in unfavorable social and cultural conditions. The contributions and perspectives of other researchers in the field that concern us are presented as well. Finally, results obtained from the investigation show the need to take action for the emotional and social benefit of these women. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has brought challenges for people with rheumatic diseases in addition to those facing the general population, including concerns about increased risks of infection with severe acute respiratory syndrome and poor coronavirus disease 2019 (COVID-19) outcomes with increased mortality. There is increasing evidence that COVID-19 can cause an alteration of the immune system with the development of autoimmune phenomena that can range from the production of autoantibodies to the appearance of autoimmune rheu- matic diseases, the main diseases being reported: vasculitis and arthritis, as well as idiopathic inflammatory myopathies, systemic lupus erythematosus and sarcoidosis, and isolated cases of systemic sclerosis and adult Still's disease. These findings highlight the potential spectrum of systemic and rheumatic autoimmune diseases that could be precipitated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. With these initial data, we try to review in the following article the clinical relationships between COVID-19 and autoimmune rheumatic diseases, as well as other data of interest such as the consequences of the pandemic with the gender of health personnel, a rigorous topical issue. The data now available suggest that rheumatic disease is associated with a small additional risk of SARS-CoV-2 infection, and that COVID-19 outcomes are primarily influenced by comorbidities and particular disease states or treatments. Despite considerable advances in our knowledge of which therapeutic agents provide benefit in COVID-19 and what constitute effective vaccination strategies, the specific considerations that apply to people with rheumatic disease have not yet been definitively addressed. An overview of the most important COVID-19 studies to date involving people with rheumatic disease may contribute to our understanding of the clinical care requirements of this population. [ABSTRACT FROM AUTHOR]

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To explore the association between T. gondii and autoimmune rheumatic diseases (ARDs). This study involved 82 patients with ARDs: 44 rheumatoid arthritis (RA), 28 systemic lupus erythematosus (SLE), and 10 systemic sclerosis (SSc) and 61 age- and sex-matched controls. Sociodemographic, clinical, and laboratory data were collected, and disease activity was assessed. Exposure to toxoplasmosis risk factors was investigated. Serological tests for anti- Toxoplasma IgM and IgG antibodies were assessed using ELISA. In SLE patients, a significant difference of T. gondii IgM versus controls was detected (P =.03). In RA and SLE patients, T. gondii IgG showed a significant difference versus controls (34 (77.3%) P =.001 and 18 (64.3%) P =.03, respectively). There was no significant difference in SSc versus controls. Fetal congenital anomalies displayed a significant difference in IgM seropositive compared to seronegative patients (P =.04). Cat exposure showed a significant difference between IgM and IgG seropositive versus seronegative patients (12 (80.0%) P =.02 and 34 (59.6) P =.04, respectively). There was no significant difference in seropositive patients regarding history of abortion, neuro-psychiatric manifestations, disease activity parameters (ESR, CRP), or different regimens of medications. Toxoplasma IgM seropositivity is associated with SLE patients. T. gondii IgG seropositivity is associated with both RA and SLE patients. However, Toxoplasma seropositivity had no association with SSc patients. An association between fetal congenital anomalies and IgM seropositivity was demonstrated. A linkage between cat exposure as a risk factor and toxoplasmosis was suggested among ARD patiants. Exploration of impact of toxoplasmosis on ARDs is a necessity through randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Malignant neoplasms are a well-recognized global public health concern, with significant impacts on human health and quality of life. The interplay between tumors and autoimmune rheumatic diseases is complex, and the resulting tumor-associated rheumatic diseases represent a rare and intricate group of conditions that occur in the context of malignant tumors. In addition, various rheumatic diseases can arise as a consequence of oncology treatment. These diseases present with intricate clinical manifestations and pathological features, often rendering them challenging to diagnose and impacting patients' quality of life. Despite this, they have yet to be fully recognized. Methods: This article presents a literature review of published original articles and review articles concerning paraneoplastic rheumatic syndromes and rheumatic diseases associated with cancer treatment. We conducted a comprehensive literature search in PubMed, Web of Science and Google Scholar databases, excluding duplicated and irrelevant studies. In cases of duplicated research, we selected articles with higher impact factors for the review. Results: This review focuses on the clinical features, diagnosis, and treatment of paraneoplastic rheumatic diseases, as well as the pathogenesis of these diseases. Additionally, we summarize the autoimmune rheumatic diseases associated with cancer treatment. Ultimately, the goal of this review is to enhance recognition and improve the management of autoimmune rheumatic diseases related to tumors. [ABSTRACT FROM AUTHOR]

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: “vitamin D, muscle, rheumatic diseases.” Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020–2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.

Abstract Introduction We assessed the risk factors and outcome of COVID-19 in patients with autoimmune rheumatic diseases(AIRD) who contracted infection while on background treatment with tofacitinib. Methods This is a non-interventional, cross-sectional, questionnaire based telephonic study which included consecutive AIRD patients on tofacitinib co-treatment. Data related to the AIRD subset, disease modifying anti rheumatic drugs(DMARDs) including glucocorticoids and comorbidities, was collected from 7 rheumatology centers across Karnataka during the second wave of COVID-19 pandemic. The information about COVID-19 occurrence and COVID-19 vaccination was recorded. Results During the study period (Jun-July 2021), 335 AIRD patients (80.6% female) on treatment with tofacitinib were included. The mean duration of tofacitinib use was 3.4+/-3.1months. Thirty-six(10.75%) patients developed COVID-19. Diabetes mellitus (p = 0.04 (OR 2.60 (1.13–5.99)) was identified as a risk factor for COVID-19 in our cohort. Almost half of our cohort was COVID-19 vaccinated with at least one dose, with resultant decline in incidence of COVID-19(OR 0.15 (0.06–0.39) among the vaccinated. Recovery amongst COVID-19 infection group was 91.2%. Conclusions The subset of AIRD patients who were on treatment with tofacitinib were found to have a higher rate of COVID-19 infection as compared to our KRACC cohort. Pre-existing comorbidity of diabetes mellitus was the significant risk factor in our cohort. This subset of the KRACC cohort shows RA patients had a lesser infection and PsA patients had a higher infection.

Abstract Objective This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. Methods Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman’s analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. Results The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. Conclusion Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.

Objective The effectiveness of COVID-19 vaccinations wanes due to immune evasion by the B.1.1.529 (Omicron) variant and diminished antibody titres over time. We aimed to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARDs). Methods This retrospective analysis included ARD patients aged 18 years or older and members of Clalit Health Services in Israel (which at the time of the study insured 52% of the entire population), and covered the period from 16 January 2022 to 31 March 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who had received three doses of the BNT162b2 vaccine (the control group) with those who had received the fourth dose. The primary outcome was COVID-19 infection, which was analysed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19–related hospitalizations and COVID-19–related death. Results We included 43 748 ARD patients, of whom 27 766 and 15 982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6942 (25.0%) of the control group and 1754 (11.0%) of the fourth dose group (P  < 0.001). Patients vaccinated with the fourth dose had a lower risk of COVID-19 infection than the entire cohort [Hazard Ratio (HR) 0.54, 95% CI 0.52, 0.58] and throughout every subgroup regardless of the baseline characteristic or medical treatment, except for rituximab. A similar association was observed for risk of COVID-19–related hospitalization (HR 0.36, 95% CI 0.22, 0.61) and of COVID-19–related death (HR 0.41, 95% CI 0.24, 0.71). Conclusion A fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared with three doses among patients with no history of COVID-19 infection. [ABSTRACT FROM AUTHOR]

Reversible cerebral vasoconstriction syndrome (RCVS) typically manifests as a sudden, severe thunderclap headache due to narrowing of the cerebral arteries. Symptoms usually resolve within three months. An imbalance in cerebral vascular tone, an abnormal endothelial function, and a decreased autoregulation of cerebral blood flow are thought to be involved in the pathogenesis of RCVS. However, the precise origin of this condition is not yet fully understood. Symptoms of Raynaud's phenomenon (RP) include vasospasm of arterioles of the digits. The pathophysiology of RP includes interactions between the endothelium, smooth muscle, and autonomic and sensory neurons that innervate arteries to help maintain vasomotor homeostasis. RP may occur before the clinical manifestation of a rheumatic condition. RCVS is rare in patients with autoimmune rheumatic disease. We describe a 54-year-old female who had a history of Raynaud's phenomenon affecting her fingers and toes since the age of 12 years. The patient was diagnosed with RCVS in 2012. She described RCVS precipitants, including the regular use of cannabis, cocaine, and amphetamine and tobacco smoking. In 2021, she presented with oral ulcers, intermittent swallowing difficulties, and Raynaud's phenomenon. Clinical examination revealed early sclerodactyly, and abnormal nail-fold capillaroscopy showed multiple giant capillaries, dilated capillary loops, and areas of capillary hemorrhage with capillary drop-out. The investigation revealed positive ANA, strongly positive SRP antibodies, and Ro60 antibodies. Our case report indicates that there may be a correlation between RCVS and Raynaud's phenomenon, and a potential connection between RCVS and autoimmune rheumatic diseases. Hence, physicians must be aware of the red flags and subtle differences in neurological abnormalities, such as headaches, in patients with autoimmune rheumatic diseases who have an inactive clinical status to improve patient care and outcomes. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Active autoimmune rheumatic diseases (ARDs) before conception increase the risk of flares and adverse pregnancy outcomes. We aimed to construct and validate a reproductive behavior questionnaire in Spanish for patients with ARDs to assess their knowledge and their reproductive behavior. Method: We constructed and validated a reproductive behavior questionnaire in two phases: (1) a literature review followed by interviews of reproductive-age female patients, and (2) a cross-sectional study to complete validation. Convenience sampling was carried out with 165 female patients: 65 participated in the cross-cultural adaptation phase and 100 in the validation phase. The internal consistency was evaluated by estimating Cronbach's alpha and tetrachoric correlation coefficients. Values ≥ 0.40 were considered acceptable (p < 0.05). Results: The initial instrument included 38 questions. Thematic analysis identified 8 important dimensions or topics, which were combined to create the Rheuma Reproductive Behavior interview questionnaire. A final total of 41 items across 10 dimensions were obtained. The test–retest analysis showed perfect correlations in 34 of the 41 items, moderate in 6 items, and negative in one of the items. The mean age of the patients was 35.65 years (SD 9.02), and the mean time to answer the survey was 13.66 min (SD 7.1). Conclusions: The Rheuma Reproductive Behavior questionnaire showed good reliability and consistency capturing patients' reproductive health knowledge and reproductive behavior. Key Points • We designed and validated a questionnaire to assess reproductive health knowledge and reproductive behavior among female patients with ARDs. • The questionnaire was comprehensible for participants, and showed good reliability and consistency capturing reproductive knowledge and behavior. • This tool may aid in the design of strategies to improve reproductive decision-making for female patients with ARDs. [ABSTRACT FROM AUTHOR]

Background and Objectives: Superb microvascular imaging is an advanced Doppler algorithm that seems to be useful in detecting low-velocity blood flow without using a contrast agent. Increasing evidence suggests that SMI is a more sensitive tool than conventional Doppler techniques for evaluating rheumatic diseases, especially inflammatory arthritis. We aimed to assess the use of SMI in evaluating joints and extraarticular structures. Materials and Methods: Two reviewers independently reviewed the literature to provide a global overview of the possibilities of SMI in rheumatology. Original English-language articles published between February 2014 and November 2022 were identified through database (PubMed, Medline, Ebsco, the Cochrane Library, and ScienceDirect) searching, and analysed to summarise existing evidence according to PRISMA methodology. Inclusion criteria covered original research articles reporting applications of SMI on rheumatic diseases and musculoskeletal disorders secondary to rheumatic conditions. Qualitative data synthesis was performed. Results: A total of 18 articles were included. No systematic reviews fulfilled our inclusion criteria. Most studies focused on characterising the synovial vascularity of rheumatoid arthritis. There have been several attempts to demonstrate SMI's value for evaluating extra-articular soft tissues (fat pads or salivary glands) and large-diameter vessels. The quantitative importance of SMI vascular indices could become a useful non-invasive diagnostic marker. Studies on therapeutic applications are still scarce, and the majority of studies have gaps in reporting the methodology (ultrasound performance technique and settings) of the research. Conclusions: SMI has proved to be useful in characterising low-flow vascularity, and growing evidence indicates that SMI is a non-invasive and lower-cost tool for prognostic assessment, especially in inflammatory arthritis. Preliminary findings also suggest potential interest in evaluating the effect of treatment. [ABSTRACT FROM AUTHOR]

• Plasma cells differ according to their origin, maturity, and among diseases. • Plasma cell alterations are common in systemic autoimmune rheumatic diseases. • Depletion of plasma cells is a promising new treatment approach. • Targeting plasma cells can be disease-specific and precise. Plasma cells are the antibody secretors of the immune system. Continuous antibody secretion over years can provide long-term immune protection but could also be held responsible for long-lasting autoimmunity in case of self-reactive plasma cells. Systemic autoimmune rheumatic diseases (ARD) affect multiple organ systems and are associated with a plethora of different autoantibodies. Two prototypic systemic ARDs are systemic lupus erythematosus (SLE) and Sjögren's disease (SjD). Both diseases are characterized by B-cell hyperactivity and the production of autoantibodies against nuclear antigens. Analogues to other immune cells, different subsets of plasma cells have been described. Plasma cell subsets are often defined dependent on their current state of maturation, that also depend on the precursor B-cell subset from which they derived. But, a universal definition of plasma cell subsets is not available so far. Furthermore, the ability for long-term survival and effector functions may differ, potentially in a disease-specific manner. Characterization of plasma cell subsets and their specificity in individual patients can help to choose a suitable targeting approach for either a broad or more selective plasma cell depletion. Targeting plasma cells in systemic ARDs is currently challenging because of side effects or varying depletion efficacies in the tissue. Recent developments, however, like antigen-specific targeting and CAR-T-cell therapy might open up major benefits for patients beyond current treatment options. [ABSTRACT FROM AUTHOR]

Abstract Purpose Autoimmune rheumatic diseases (ARD) are groups of diseases that are commonly associated with cardiac and pulmonary manifestations and may affect the morbidity and mortality of the patients. The study aimed to the assessment of cardiopulmonary manifestations and their correlation with the semi-quantitative scoring of high-resolution computed tomography (HRCT) in ARD patients. Methods and patients 30 patients with ARD were included in the study (mean age 42.2 ± 9.76 years) [10 patients were scleroderma (SSc), 10 patients were rheumatoid arthritis (RA), and 10 patients were systemic lupus erythematosus (SLE)]. They all met the diagnostic criteria of the American College of Rheumatology and underwent spirometry, echocardiography, and chest HRCT. The HRCT was assessed by a semi-quantitative score for parenchymal abnormalities. Correlation between HRCT lung scores and: inflammatory markers, lung volumes in spirometry, and echocardiographic indices has been performed. Results The total lung score (TLS) by HRCT was 14.8 ± 8.78 (mean ± SD), ground glass opacity score (GGO) was 7.20 ± 5.79 (mean ± SD) and fibrosis lung score (F) was 7.63 ± 6.05 (mean ± SD). TLS correlated significantly with ESR (r 0.528, p 0.003), CRP (r 0.439, p 0.015), PaO2 (r -0.395, P 0.031) FVC% (r -0.687, p 0.001), and echocardiographic Tricuspid E (r -0.370, p 0.044), Tricuspid E/è (r -0.397,p 0.03), ESPAP (r 0.459,p 0.011), TAPSE (r -0.405, p 0.027), MPI-TDI (r -0.428, p 0.018) and RV Global strain(r -0.567, p 0.001). GGO score correlated significantly with ESR (r 0.597, p 0.001), CRP (r 0.473, p 0.008), FVC% (r -0.558, p 0.001), and RV Global strain(r -0.496, p 0.005). F score correlated significantly with FVC% (r -0.397, p 0.030), Tricuspid E/è (r -0.445, p 0.014), ESPAP (r 0.402, p 0.028), and MPI-TDI (r -0.448, p 0.013). Conclusion The total lung score and GGO score in ARD were found to be consistently significantly correlated with FVC% predicted, PaO2, inflammatory markers, and RV functions. Fibrotic score correlated with ESPAP. Therefore, in a clinical setting, most clinicians who monitor patients suffering from ARD should concern with the applicability of semiquantitative HRCT scoring in clinical practice.

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs’ diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.

Introduction: Safety of rituximab (RTX) in autoimmune rheumatic diseases (AIRDs) has been a concern during this ongoing coronavirus (COVID-19) pandemic. Delayed worsening of COVID symptoms, increased hospital stays, and mortality has been reported among those infected post-RTX. This study describes the occurrence and course of COVID-19 infection among AIRD Indian patients who received RTX during this pandemic. Patients and Methods: Adult patients (=18 years) with any AIRD, who received RTX between October 2019 and May 2021, were enrolled in this study. Patients satisfying the inclusion criteria were telephonically enquired about contracting confirmed COVID-19, its course, treatment, and outcome. Baseline parameters, immunoglobulin G level, vaccination, and comorbidity status before RTX were compared between the COVID-19 infected and noninfected patients to determine factors affecting the outcome. Results: Out of 1081 patients admitted during the study period, 218 patients received RTX. The mean age of these patients was 40.1 ± 14.2 years and comprised mostly of women (81.7%). Rheumatoid arthritis followed by lupus and anti-neutrophilic cytoplasmic antibodies-associated vasculitis was the predominant AIRD. Among the patients contacted (207/218 [94.9%]), 11 (5.3%) patients reported confirmed COVID-19 infections. Out of these, three (27.3%) had severe COVID-19 and one patient succumbed to it. Others became symptom-free after a mean duration of 14.4 ± 4.7 days of onset of symptoms. No significant difference among the baseline parameters observed predicted COVID-19 susceptibility. Conclusion: Among our AIRD patients treated with RTX, occurrence, and mortality of COVID-19 infection was low. Younger age of our patient cohort and female predominance might have contributed in reducing the severity of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. Methods: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman’s analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. Results: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. Conclusion: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients. [ABSTRACT FROM AUTHOR]

Dry eye disease is a chronic disease of the ocular surface characterized by abnormal tear film composition, tear film instability, and ocular surface inflammation, affecting 5% to 50% of the population worldwide. Autoimmune rheumatic diseases (ARDs) are systemic disorders with multi-organ involvement, including the eye, and play a significant role in dry eye. To date, most studies have focused on Sjögren's syndrome (one of the ARDs) since it manifests as two of the most common symptoms–dry eyes and a dry mouth-and attracts physicians to explore the relationship between dry eye and ARDs. Many patients complained of dry eye related symptoms before they were diagnosed with ARDs, and ocular surface malaise is a sensitive indicator of the severity of ARDs. In addition, ARD related dry eye is also associated with some retinal diseases directly or indirectly, which are described in this review. This review also summarizes the incidence, epidemiological characteristics, pathogenesis, and accompanying ocular lesions of ARD's related dry eye, emphasizing the potential role of dry eye in recognition and monitoring among ARDs patients. [ABSTRACT FROM AUTHOR]

Autoimmune rheumatic diseases are a cluster of heterogeneous disorders that share some clinical symptoms such as pain, tissue damage, immune deregulation, and the presence of inflammatory mediators. Biologic disease-modifying antirheumatic drugs are some of the most effective treatments for rheumatic diseases. However, their molecular and pharmacological complexity makes them potentially immunogenic and capable of inducing the development of anti-drug antibodies. TNF inhibitors appear to be the main contributors to immunogenicity because they are widely used, especially in rheumatoid arthritis. Immunogenicity response on these treatments is crucial since the appearance of ADAs has consequences in terms of safety and efficacy. Therefore, this review proposes an overview of the immunogenicity of biological agents used in autoimmune rheumatic diseases highlighting the prevalence of anti-drug antibodies. [ABSTRACT FROM AUTHOR]

Introduction: Safety of rituximab (RTX) in autoimmune rheumatic diseases (AIRDs) has been a concern during this ongoing coronavirus (COVID-19) pandemic. Delayed worsening of COVID symptoms, increased hospital stays, and mortality has been reported among those infected post-RTX. This study describes the occurrence and course of COVID-19 infection among AIRD Indian patients who received RTX during this pandemic. Patients and Methods: Adult patients (≥18 years) with any AIRD, who received RTX between October 2019 and May 2021, were enrolled in this study. Patients satisfying the inclusion criteria were telephonically enquired about contracting confirmed COVID-19, its course, treatment, and outcome. Baseline parameters, immunoglobulin G level, vaccination, and comorbidity status before RTX were compared between the COVID-19 infected and noninfected patients to determine factors affecting the outcome. Results: Out of 1081 patients admitted during the study period, 218 patients received RTX. The mean age of these patients was 40.1 ± 14.2 years and comprised mostly of women (81.7%). Rheumatoid arthritis followed by lupus and anti-neutrophilic cytoplasmic antibodies-associated vasculitis was the predominant AIRD. Among the patients contacted (207/218 [94.9%]), 11 (5.3%) patients reported confirmed COVID-19 infections. Out of these, three (27.3%) had severe COVID-19 and one patient succumbed to it. Others became symptom-free after a mean duration of 14.4 ± 4.7 days of onset of symptoms. No significant difference among the baseline parameters observed predicted COVID-19 susceptibility. Conclusion: Among our AIRD patients treated with RTX, occurrence, and mortality of COVID-19 infection was low. Younger age of our patient cohort and female predominance might have contributed in reducing the severity of SARS-CoV-2 infection.

Purpose: Autoimmune rheumatic diseases (ARD) are groups of diseases that are commonly associated with cardiac and pulmonary manifestations and may affect the morbidity and mortality of the patients. The study aimed to the assessment of cardiopulmonary manifestations and their correlation with the semi-quantitative scoring of high-resolution computed tomography (HRCT) in ARD patients. Methods and patients: 30 patients with ARD were included in the study (mean age 42.2 ± 9.76 years) [10 patients were scleroderma (SSc), 10 patients were rheumatoid arthritis (RA), and 10 patients were systemic lupus erythematosus (SLE)]. They all met the diagnostic criteria of the American College of Rheumatology and underwent spirometry, echocardiography, and chest HRCT. The HRCT was assessed by a semi-quantitative score for parenchymal abnormalities. Correlation between HRCT lung scores and: inflammatory markers, lung volumes in spirometry, and echocardiographic indices has been performed. Results: The total lung score (TLS) by HRCT was 14.8 ± 8.78 (mean ± SD), ground glass opacity score (GGO) was 7.20 ± 5.79 (mean ± SD) and fibrosis lung score (F) was 7.63 ± 6.05 (mean ± SD). TLS correlated significantly with ESR (r 0.528, p 0.003), CRP (r 0.439, p 0.015), PaO2 (r -0.395, P 0.031) FVC% (r -0.687, p 0.001), and echocardiographic Tricuspid E (r -0.370, p 0.044), Tricuspid E/è (r -0.397,p 0.03), ESPAP (r 0.459,p 0.011), TAPSE (r -0.405, p 0.027), MPI-TDI (r -0.428, p 0.018) and RV Global strain(r -0.567, p 0.001). GGO score correlated significantly with ESR (r 0.597, p 0.001), CRP (r 0.473, p 0.008), FVC% (r -0.558, p 0.001), and RV Global strain(r -0.496, p 0.005). F score correlated significantly with FVC% (r -0.397, p 0.030), Tricuspid E/è (r -0.445, p 0.014), ESPAP (r 0.402, p 0.028), and MPI-TDI (r -0.448, p 0.013). Conclusion: The total lung score and GGO score in ARD were found to be consistently significantly correlated with FVC% predicted, PaO2, inflammatory markers, and RV functions. Fibrotic score correlated with ESPAP. Therefore, in a clinical setting, most clinicians who monitor patients suffering from ARD should concern with the applicability of semiquantitative HRCT scoring in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. Methods: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. Results: Through the study period (April–December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. Conclusion: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort. [ABSTRACT FROM AUTHOR]

Data on the risk of adverse events (AEs) and disease flares in autoimmune rheumatic diseases (ARDs) after the third dose of COVID-19 vaccine are scarce. The aim of this multicenter, prospective study is to analyze the clinical and immunological safety of BNT162b2 vaccine in a cohort of rheumatoid arthritis (RA) patients followed-up from the first vaccine cycle to the third dose. The vaccine showed an overall good safety profile with no patient reporting serious AEs, and a low percentage of total AEs at both doses (40/78 (51.3%) and 13/47 (27.7%) patients after the second and third dose, respectively (p < 0.002). Flares were observed in 10.3% of patients after the end of the vaccination cycle and 12.8% after the third dose. Being vaccinated for influenza was inversely associated with the onset of AEs after the second dose, at both univariable (p = 0.013) and multivariable analysis (p = 0.027). This result could allow identification of a predictive factor of vaccine tolerance, if confirmed in larger patient populations. A higher disease activity at baseline was not associated with a higher incidence of AEs or disease flares. Effectiveness was excellent after the second dose, with only 1/78 (1.3%) mild breakthrough infection (BI) and worsened after the third dose, with 9/47 (19.2%) BI (p < 0.002), as a probable expression of the higher capacity of the Omicron variants to escape vaccine recognition. [ABSTRACT FROM AUTHOR]

Immunogenicity data on the mRNA SARS-CoV-2 vaccine booster after completing a primary series vaccination, other than the mRNA vaccine, in patients with autoimmune rheumatic diseases (ARDs) is scarce. In this study, we reported the humoral immunogenicity of an mRNA booster 90–180 days after completing heterologous CoronaVac/ChAdOx1 nCoV-19 (n = 19) or homologous ChAdOx1 nCoV-19 (n = 14) vaccination by measuring the anti-SARS-CoV-2 receptor binding domain (RBD) IgG levels at one and three months after mRNA booster vaccination. This study included 33 patients with ARDs [78.8% women; mean (SD) age: 42.9 (10.6) years]. Most patients received prednisolone (75.8%, mean [IQR] daily dose: 7.5 [5, 7.5] mg) and azathioprine (45.5%). The seropositivity rates were 100% and 92.9% in CoronaVac/ChAdOx1 and ChAdOx1/ChAdOx1, respectively. The median (IQR) anti-RBD IgG level was lower in the ChAdOx1/ChAdOx1 group than in the CoronaVac/ChAdOx1 group (1867.8 [591.6, 2548.6] vs. 3735.8 [2347.9, 5014.0] BAU/mL, p = 0.061). A similar trend was significant in the third month [597.8 (735.5) vs. 1609.9 (828.4) BAU/mL, p = 0.003]. Minor disease flare-ups occurred in 18.2% of the patients. Our findings demonstrated satisfactory humoral immunogenicity of mRNA vaccine boosters after a primary series, with vaccine strategies other than the mRNA platform. Notably, the vaccine-induced immunity was lower in the ChAdOx1/ChAdOx1 primary series. [ABSTRACT FROM AUTHOR]

Several autoimmune rheumatic diseases (ARD) are responsible for the increased risk of cardiovascular comorbidities, whether due to atherosclerosis, thrombus formation, vasculitis or myocardial inflammation. The improvement of therapeutic practices and the increase in life expectancy of patients brought a new look at cardiovascular complications resulting from rheumatological disorders. This article considers heart disease in Rheumatic Diseases. The results demonstrated that physical activity is one of the most important behavioral interventions, as a beneficial impact on the probability of developing, suffering symptomatically or dying from CVD. Thus, maintaining a healthy lifestyle reduces risk factors for CVD, including obesity, dyslipidemia, hypertension, diabetes mellitus and possibly even inflammation. It also showed efficacy in preventing acute coronary syndromes. Exercise seems to help manage established CVDs, be it aerobic exercise or resistance training. They improve myocardial contractility and quality of life in patients with chronic heart failure. [ABSTRACT FROM AUTHOR]

BackgroundWhile autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history.MethodsWomen with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis.ResultsOf the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups.ConclusionsAmong women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.

OBJECTIVES: Autoimmune rheumatic diseases (ARDs) affect women of childbearing age and have been associated with adverse birth outcomes. The impact of diseases like ankylosing spondylitis and psoriatic arthritis (PsA) on birth outcomes remains less studied to date. Our objective was to evaluate the impact of ARDs on preterm birth (PTB), congenital anomalies, low birth weight (LBW) and small for gestational age (SGA), in a large cohort of women. METHODS: We conducted a propensity score-matched analysis to predict ARD from a retrospective birth cohort of all live, singleton births in California occurring between 2007 and 2012. Data were derived from birth certificate records linked to hospital discharge International Classification of Diseases, ninth revision codes. RESULTS: We matched 10 244 women with a recorded ARD diagnosis (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, PsA); ankylosing spondylitis and juvenile idiopathic arthritis (JIA) to those without an ARD diagnosis. The adjusted OR (aOR) of PTB was increased for women with any ARD (aOR 1.93, 95% CI 1.78 to 2.10) and remained significant for those with RA, SLE, PsA and JIA. The odds of LBW and SGA were also significantly increased among women with an ARD diagnosis. ARDs were not associated with increased odds of congenital anomalies. CONCLUSION: Consistent with prior literature, we found that women with ARDs are more likely to have PTB or deliver an SGA infant. Some reassurance is provided that an increase in congenital anomalies was not found even in this large cohort.

Abstract Background We examined attitudes toward the COVID‐19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods A multicenter, web‐based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results Of the unvaccinated patients, 32.9% were willing to receive the COVID‐19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine‐related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID‐19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow‐up of 88 (38, 131) days, patients' disease activities were stable. Conclusions The findings show that AIIRD patients were unwilling to receive the COVID‐19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID‐19 disease and vaccines had a significant effect on vaccination willingness.

Abstract Background We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). Methods This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. Results COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5–20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p

Background: Cyclophosphamide (CYC) has known cytotoxic effects on ovarian reserve and has been linked to premature ovarian failure (POF) in systemic lupus erythematosus (SLE). The concurrent use of gonadotropin-releasing hormone agonists (GnRHas) is postulated to preserve ovarian function by reducing the number of follicles exposed to CYC, but there is paucity of data to establish its efficacy. We conducted a meta-analysis to summarize the effect of concurrent GnRHa use in persevering ovarian function and pregnancy. Methods: English language databases of PubMed, Embase, and Cochrane were searched to include studies published between 2000 and 2021. Studies in females with rheumatic diseases receiving concurrent GnRHa and CYC therapy to evaluate ovarian preservation as defined by amenorrhea, follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), or estradiol levels or successful pregnancy were included. We used a fixed effect, exact, Mantel-Haenszel approach to estimate the overall odds ratio (OR) and associated 95% confidence intervals (95% CIs). Results: Seven studies with 218 female patients were included. The ovarian function was preserved in 125/132 (94.6%) of women who received GnRHa concurrently with CYC compared to 50/86 (58%) of women who did not receive GnRHa (OR = 10.3, CI = 4.83–36.29). The OR for pregnancy with GnRHa use = 2.94 (CI = 1.04–9.89). Conclusion: Our results based on limited published studies suggest that concurrent GnRHa use preserves ovarian function and increase odds of pregnancy. It can be considered for premenopausal SLE females receiving CYC. Long-term follow-up studies are needed to establish the efficacy and safety of GnRHa use for ovarian preservation. [ABSTRACT FROM AUTHOR]